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Journal of the European Academy of... Feb 2023Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the...
BACKGROUND
Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the synthesis of cholesterol, an essential component for the formation of the extracellular lipid lamellae in the stratum corneum. Porokeratosis is reportedly associated with an increased risk of keratinocyte cancer, but to date, no large epidemiological studies have been conducted to further address this association.
OBJECTIVES
The first objective was to characterize a cohort of patients diagnosed with porokeratosis at the Department of Dermatology and Venereology, Sahlgrenska University Hospital (SU), Gothenburg, Sweden. The second objective was to conduct a nationwide registry-based cohort study to investigate the association, if any, between porokeratosis and the cutaneous malignancies squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma.
METHODS
For the SU cohort, the hospital registry was searched for patients with a diagnosis of porokeratosis recorded between 2016 and 2020. Clinical data were extracted from the records of the identified patients. For the nationwide cohort, national registries were searched to identify patients with a diagnosis of porokeratosis between 2001 and 2020. A tenfold control cohort was formed by Statistics Sweden. The data was cross-referenced with the Swedish Cancer Register to study the associations between porokeratosis and SCC, BCC and melanoma.
RESULTS
Disseminated superficial actinic porokeratosis was the most common clinical type among the 108 patients in the SU cohort. In the nationwide search, 2277 patients with porokeratosis were identified (prevalence 1/4132). Porokeratosis was associated with an increased risk for SCC, BCC and melanoma with hazard ratios (95% CI) of 4.3 (3.4-5.4), 2.42 (1.97-2.98) and 1.83 (1.18-2.82), respectively, in the patient cohort, compared to the matched control group.
CONCLUSION
Porokeratosis is a common genodermatosis, and it is associated with an enhanced risk of skin cancer.
Topics: Humans; Porokeratosis; Cohort Studies; Melanoma; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Keratinocytes
PubMed: 36152004
DOI: 10.1111/jdv.18587 -
Anais Brasileiros de Dermatologia 2022Although dermatofibromas are not uncommon benign dermal nodules, palms are rarely involved. Herein, a rare case of palmar dermatofibroma was described, which occurred in...
Although dermatofibromas are not uncommon benign dermal nodules, palms are rarely involved. Herein, a rare case of palmar dermatofibroma was described, which occurred in a patient with porokeratosis.
Topics: Histiocytoma, Benign Fibrous; Humans; Porokeratosis; Skin Neoplasms
PubMed: 36109270
DOI: 10.1016/j.abd.2021.07.008 -
Indian Journal of Dermatology 2022
PubMed: 36092224
DOI: 10.4103/ijd.ijd_702_21 -
Cureus Jul 2022Linear porokeratosis is a cutaneous disorder that typically presents in a unilateral linear formation. While the exact cause of linear porokeratosis is unknown, it is...
Linear porokeratosis is a cutaneous disorder that typically presents in a unilateral linear formation. While the exact cause of linear porokeratosis is unknown, it is thought to be a downstream effect of disrupted cholesterol synthesis and mevalonate accumulation. Our patient is a 61-year-old male with an unusual case presentation of bilateral linear porokeratosis. He had failed numerous standard therapies. Pathologic examination of a skin biopsy was consistent with bilateral linear porokeratosis. Through a PubMed search, there have been limited reported cases of unilateral linear porokeratosis, but there have not been any reported cases of bilateral linear porokeratosis. There are currently limited therapies with satisfactory outcomes for variants of porokeratosis. While there are some studies on the topical application of cholesterol/lovastatin, limited studies have been performed on the linear form. Our study evaluates the efficacy of compounded topical cholesterol 2%/lovastatin 2% ointment on bilateral linear porokeratosis. The patient demonstrated a significant reduction of porokeratotic lesions on the treated arm compared to the untreated arm. Cholesterol/lovastatin is alternative therapy that can be considered in the treatment of linear porokeratosis and other porokeratosis variants.
PubMed: 36060323
DOI: 10.7759/cureus.27540 -
Frontiers in Pharmacology 2022Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate... (Review)
Review
Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate wavelength. It is a non-invasive therapeutic procedure widely used in oncodermatology for treatment of numerous skin cancers, but in the last years its use has been gradually extended to an increasing list of skin diseases of both infectious and inflammatory nature. Although PDT is proven as a safe and effective therapeutic option in adults, its use is not well standardized in the pediatric population. In this review, we will focus on clinical applications, mechanisms of action, protocols, and adverse events in children and adolescents. Most of pediatric experiences concerned treatment of skin cancers in Gorlin syndrome and xeroderma pigmentosum, acne vulgaris, and viral warts, but other applications emerged, such as cutaneous lymphoma and pseudo-lymphomas, necrobiosis lipoidica, hidradenitis suppurativa, dissecting cellulitis, leishmaniasis, angiofibromas, verrucous epidermal nevus, and linear porokeratosis. In these pediatric diseases, PDT appeared as an effective therapeutic alternative. The results on vitiligo were limited and not fully encouraging. Although highly versatile, PDT is not a therapy for all skin diseases, and a deeper knowledge of its mechanisms of action is required to better define its spectrum of action and safety in pediatric patients.
PubMed: 36052131
DOI: 10.3389/fphar.2022.879380 -
The Journal of Investigative Dermatology Sep 2022Mosaicism results from postzygotic alterations during embryogenesis leading to genetically distinct populations of cells within individuals and has been historically...
Mosaicism results from postzygotic alterations during embryogenesis leading to genetically distinct populations of cells within individuals and has been historically recognized by phenotypes with visible, often patterned manifestations. Before the advent of molecular profiling assays and high-throughput sequencing, it was challenging to study mosaicism in human disease; however, the study of mosaic disorders has recently revealed unexpected and novel pathways for disease pathogenesis. In this paper, we will review the techniques for discovery of disease-causing alleles using Proteus syndrome; phakomatosis pigmentokeratotica; linear porokeratosis; and vacuoles, E1 enzyme, X-linked, autoinflammatory somatic syndrome as models. These tools represent powerful approaches for dissecting the genetic basis for human disorders.
Topics: Alleles; High-Throughput Nucleotide Sequencing; Humans; Mosaicism; Nevus, Pigmented; Proteus Syndrome; Skin Diseases, Genetic
PubMed: 35985765
DOI: 10.1016/j.jid.2022.07.001 -
Cureus Jul 2022Porokeratosis describes a heterogenic group of keratinization disorders in which lesions are papules and plaques that demonstrate central atrophy surrounded by a...
Porokeratosis describes a heterogenic group of keratinization disorders in which lesions are papules and plaques that demonstrate central atrophy surrounded by a hyperkeratotic margin. Clinical variants include not only porokeratosis of Mibelli, but also disseminated superficial, disseminated actinic superficial, linear, punctate, and palmaris et plantaris disseminata. Porokeratosis has a risk of malignant transformation. A woman with disseminated superficial actinic porokeratosis (DSAP) whose lesions presented as pruritic plaques and papules is described. The diagnosis was suspected clinically, supported by dermoscopy findings, and confirmed histologically. The condition-associated pruritus was managed symptomatically; her skin lesions will be monitored clinically. Clinical manifestations, dermatoscopic features, pathology findings, and treatment options for DSAP are summarized.
PubMed: 35983404
DOI: 10.7759/cureus.26923 -
Pediatric Dermatology Nov 2022Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of...
BACKGROUND
Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported.
OBJECTIVE
To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN.
METHODS
We recruited patients diagnosed with ILVEN based on clinical and histopathological criteria. Exome sequencing of affected skin with or without blood/saliva was performed and germline and somatic pathogenic variants were identified.
RESULTS
Five patients were enrolled. All had skin lesions from birth or early childhood. Two patients developed psoriasis vulgaris after the diagnosis of ILVEN. The first had a germline heterozygous CARD14 mutation and a post-zygotic hotspot mutation in KRT10. The histopathologic evaluation did not show epidermolytic hyperkeratosis. The second had a post-zygotic hotspot mutation in HRAS. Her ILVEN became itchy once psoriasis developed. One patient was re-diagnosed with linear porokeratosis based on a germline mutation in PMVK and a post-zygotic second-hit mutation. Two patients were re-diagnosed with congenital hemidysplasia with ichthyosiform nevus and limb defect nevus based on germline NSDHL mutations.
CONCLUSION
ILVEN is a clinical descriptor for a heterogenous group of mosaic inflammatory disorders. Genetic analysis has the potential to more precisely categorize ILVEN and permits pathogenesis-directed therapies in some cases.
Topics: Female; Humans; Child, Preschool; Nevus, Sebaceous of Jadassohn; Skin Neoplasms; Nevus; Nevus, Pigmented; Psoriasis; Skin Diseases; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; 3-Hydroxysteroid Dehydrogenases
PubMed: 35853659
DOI: 10.1111/pde.15094 -
Genes & Diseases Jul 2022Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate... (Review)
Review
Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions, all resulting from pathogenic variants in the mevalonate kinase gene (). Their clinical manifestations are highly variable, ranging from more or less serious systemic disorders, such as hereditary recurrent fevers, to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria, and the most recent is disseminated superficial actinic porokeratosis, a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for -associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology, then summarizes and compares the different genetic mechanisms involved in this group of disorders, and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.
PubMed: 35685471
DOI: 10.1016/j.gendis.2021.05.002 -
Skin Health and Disease Mar 2022Porokeratosis (PK) is considered a skin-specific autoinflammatory keratinization disease. Intriguingly, four causative genes of PK are in turn arranged in mevalonate...
BACKGROUND
Porokeratosis (PK) is considered a skin-specific autoinflammatory keratinization disease. Intriguingly, four causative genes of PK are in turn arranged in mevalonate pathway, with variants being the commonest followed by variants in a cohort of Chinese patients. Evidence indicates that mevalonate metabolites induce trained immunity in human monocytes and regulate T cells at multiple levels. Of note, γδT cells are dually regulated by intracellular and extracellular mevalonate metabolism.
AIMS
To identify the possible differences in T-cell between or variants from PK patients.
MATERIALS & METHODS
Targeted exome sequencing and exonic CNV screening were performed in 26 patients with PK. Sanger sequencing was used to validate all identified variants. Among them, 22 patients were identified with or variants. PBMCs from 22 PK patients and 27 normal controls (NCs) were analysed by flow cytometry for the frequencies of T cells subsets, including IFN-γ-, and TNF-α-producing T cells.
RESULTS
There were 14 mutations identified in the 26 PK patients, including 6 novel mutations (: c.118_226+1337dup, c.388_392delGATATinsC, c.613A>T, c.768G>C, and : c.250C>T, c.988T>G). In contrast to NCs, significantly decreased frequencies of CD8 and Vγ9Vδ2 T cells were observed in the PK patients with variants. Moreover, it was found that dysregulated secretion of pro-inflammatory cytokines by T cells in both PK patients with and variants.
CONCLUSIONS
Our findings enriched the Human Gene Mutation Databases and showed probable differences in peripheral T cells subsets between PK patients and controls.
PubMed: 35665211
DOI: 10.1002/ski2.82